Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Histol Histopathol. 2013 Apr;28(4):531-42. doi: 10.14670/HH-28.531. Epub 2013 Feb 7.
BACKGROUND/AIM: Autophagy has dual roles in tumorigenesis: tumor-promoting or tumor-suppressing. The aim of the present study was to examine autophagy-related markers by immunohistochemistry in gastric carcinoids and adenocarcinomas in rodent models and patients.
Gastric carcinoids in Mastomys were induced by loxtidine treatment. Spontaneously developed gastric adenocarcinomas in Japanese cotton rats and INS-GAS transgenic mice were included. Patient tissue samples of gastric carcinoids or adenocarcinomas were collected. Immunohistochemistry was performed against autophagy-related gene protein-6 (ATG-6, also called beclin-1), ATG-5 and ATG-16.
In tumor-free Mastomys, ATG-5, ATG-16 and beclin-1 were immunepositive in the gastric mucosa. In tumor-bearing Mastomys, ATG-5 and ATG-16 were negative in the tumors, whereas beclin-1 was positive in four of five animals. In carcinoid patients, ATG-5 was negative in six of ten, ATG-16 negative in nine of ten, and beclin-1 negative in three of ten patients. In cotton rats, ATG-5 and ATG-16 were negative in all tumors. Beclin-1 was negative in three of five rats. In INS-GAS mice, ATG-5 and beclin-1 were positive in the tumor area, but the numbers of immunopositive cells per gland were reduced by about 50% in comparison with wild-type mice. In adenocarcinoma patients, ATG-5 and ATG-16 were negative in eight of ten, and beclin-1 positive in all ten patients.
An impaired autophagy took place at the stage of formation of ATG-5-ATG-12-ATG-16 complex in both gastric carcinoids and adenocarcinoma of both rodent models and patients. ATG-5 and ATG-16 might be better markers than beclin-1 in assessing autophagy in these lesions.
背景/目的：自噬在肿瘤发生中具有双重作用：促进肿瘤或抑制肿瘤。本研究旨在通过免疫组织化学检测啮齿动物模型和患者胃类癌和腺癌中的自噬相关标志物。
用洛替丁处理 Mastomys 诱导胃类癌。纳入自发性发展的日本棉鼠胃腺癌和 INS-GAS 转基因小鼠。收集胃类癌或腺癌患者组织样本。对自噬相关基因蛋白-6（ATG-6，也称为 beclin-1）、ATG-5 和 ATG-16 进行免疫组织化学检测。
在无肿瘤的 Mastomys 中，胃黏膜中 ATG-5、ATG-16 和 beclin-1 呈免疫阳性。在荷瘤 Mastomys 中，肿瘤中 ATG-5 和 ATG-16 阴性，而 beclin-1 在 5 只动物中的 4 只呈阳性。在类癌患者中，ATG-5 在 10 例中的 6 例中阴性，ATG-16 在 10 例中的 9 例中阴性，beclin-1 在 10 例中的 3 例中阴性。在棉鼠中，ATG-5 和 ATG-16 在所有肿瘤中均为阴性。beclin-1 在 5 只大鼠中 3 只阴性。在 INS-GAS 小鼠中，肿瘤区域 ATG-5 和 beclin-1 呈阳性，但与野生型小鼠相比，每个腺体的免疫阳性细胞数量减少了约 50%。在腺癌患者中，ATG-5 和 ATG-16 在 10 例中的 8 例中阴性，beclin-1 在 10 例中阳性。
在啮齿动物模型和患者的胃类癌和腺癌中，自噬在形成 ATG-5-ATG-12-ATG-16 复合物的阶段受到抑制。与 beclin-1 相比，ATG-5 和 ATG-16 可能是评估这些病变中自噬的更好标志物。
